Following reports on potential risks of hydroquinone (HQ), HQ for skin lightening has been banned or restricted in Europe and the US. In contrast, HQ is not listed as a prohibited or limited ingredient for cosmetic use in Japan, and many HQ cosmetics are sold without restriction. To assess the risk of systemic effects of HQ we examined the rat skin permeation rates of four HQ (0.3%, 1.0%, 2.6%, and 33%) cosmetics. The permeation coefficients ranged from 1.2 x 10(-9) to 3.1 x 10(-7) cm/s, with the highest value superior than the HQ aqueous solution (1.6 x 10(-7) cm/s). After dermal application of the HQ cosmetics to rats, HQ in plasma was detected only in the treatment by highest coefficient cosmetic. Absorbed HQ levels treated with this highest coefficient cosmetic in humans were estimated by numerical methods, and we calculated the margin of exposure (MOE) for the estimated dose (0.017 mg/kg-bw/day in proper use) to a benchmark dose for rat renal tubule adenomas. The MOE of 559 is judged to be in a range safe for the consumer. However, further consideration may be required for regulation of cosmetic ingredients. (C) 2016 Elsevier Inc. All rights reserved.